Compressed tablets (e.g., caplets) are known as one of the most cost effective, consumer friendly and convenient dosage forms available for delivering pharmaceutically active agents. Compressed tablets often involve multiple steps in order to incorporate pharmaceutically active agents into the form since only certain materials may be used for compression. The materials must have the correct compression characteristics such as flow and compressibility in order to maintain operability on a tablet press, retain shape and form without breakage, and dissolve within an appropriate timeframe in the gastrointestinal tract. In order to achieve these characteristics, blends or powdered materials must often be granulated using high shear, chilsonation, or fluid bed techniques to increase the size and maintain a flowable particle shape. Methods for direct compression and wet granulation processes are known in the art, and are described in detail in, for example, Lachman, et al., The Theory and Practice of Industrial Pharmacy, Chapter 11 (3rd ed. 1986).
Traditional granulation techniques present additional challenges when a dosage form must be prepared with multiple pharmaceutically active agents. In many cases, it may be desired to combine large dose pharmaceutically active agents, such as acetaminophen, with smaller dose pharmaceutically active agents, such as chlorpheniramine or dextromethorphan. In order to achieve this, multiple types of granulations must often be prepared at a manufacturing scale, which increases cost and complexity. In addition to these challenges with granulation, the pharmaceutical industry has actively progressed in developing pharmaceutically active agents that require smaller and smaller doses, to the point where it is not uncommon for such agents to be administered at less than 1 microgram per dose. However, as the dose of the pharmaceutically active agent becomes smaller, the size of the tablet that is administered still remains relatively the same for ease of handling and swallowing. Therefore, in order to maintain uniformity of the agent within the compression blend, multiple blending steps are often required prior to compression.
The present invention provides for an improved method of manufacturing a tablet containing a pharmaceutically active agent by injecting a liquid drug composition containing the pharmaceutically active agent into the die cavity. The invention can provide for improved content uniformity in tablets that contain small quantities of pharmaceutically active agents, as liquid solutions are generally more uniform than powder mixtures. The invention also provides for the advantage of delivering to each tablet a precise quantity of pharmaceutically active agents, which can be difficult to achieve by conventional dry blending methodologies. Moreover, the present invention also can allow for greater efficiency and a more rapid change over between the manufacture of different tablets as a simple direct compression tablet base can be used for many different liquid injected pharmaceutically active agents.